Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

BACKGROUND: Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. PURPOSE: To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. STUDY TYPE: Retrospective. POPULATION: Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. ASSESSMENT: EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. STATISTICAL TESTS: Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. RESULTS: EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). DATA CONCLUSION: The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report.

BACKGROUND: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient. CASE PRESENTATION: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. CONCLUSIONS: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.

Diagnosis of single umbilical artery and risk of foetal congenital malformations by prenatal ultrasound: a retrospective study.

BACKGROUND: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. METHODS: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. RESULTS: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. CONCLUSIONS: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.

A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Giant Intrauterine Mass Because of Puerperal Infection: A Case Report.

Background: Puerperal infection is one of the four main causes of maternal mortality. A giant intrauterine mass caused by puerperal infection is a rare form of infection. The delay in treatment may result in the removal of the uterus. Case Presentation: We report a case of a large intrauterine mass resulting from puerperal infection, in which the uterus was salvaged through antibiotic treatment and curettage. The patient was a 27-year-old female, who presented with a large intrauterine mass, accompanied by fever and abdominal pain 35 days after vaginal delivery. The large intrauterine mass was ultimately pathologically confirmed to be necrotic smooth muscle tissue instead of residual pregnancy tissue. Conclusion: In most cases, the intrauterine mass after pregnancy is residual pregnancy tissue. Early identification and management are critical to ensure a good prognosis for patients. Obstetricians and pregnant women should be fully aware of the hazards of puerperal infections.

The association between the dietary inflammatory index and allergic rhinitis: a case-control study.

Background and objective: Allergic rhinitis (AR) is a common chronic inflammatory disease that significantly impacts the quality of life of patients. However, there is limited research on the relationship between the Dietary Inflammatory Index (DII) and the risk of AR. Our study aimed to assess the association between DII and AR in a sample of adults from North China. Methods: In a case-control study, we selected 166 cases of AR and 166 age- and gender-matched controls. Dietary intake was assessed using a validated food frequency questionnaire. The energy-adjusted DII (E-DII) scores were calculated based on the quantity of diet components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between E-DII and AR. Results: Our findings indicate a positive correlation between E-DII and AR risk. After controlling for confounders, individuals in the highest E-DII tertile exhibited a 4.41-fold increased risk of AR compared to those in the lowest tertile (OR 4.41, 95% CI 2.31-8.41). Additionally, stratified analysis showed that E-DII was positively associated with AR subtype (seasonal vs. perennial), duration (≤6 years vs. >6 years), severity (mild vs. moderate-severe), and onset time (intermittent vs. persistent). Furthermore, individuals in the highest E-DII tertile had higher intake of total fat, SFA, PUFAs, and n-6 PUFAs. Conclusion: In conclusion, we realized that there is a positive association between the E-DII score and AR. The consumption of diets abundant in anti-inflammatory nutrients and low in pro-inflammatory nutrient contents is recommended as a preventative strategy against AR.

Transcriptomic profile of premature ovarian insufficiency with RNA-sequencing.

Introduction: This study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression. Methods: A total of sixty-one women, comprising 31 individuals with POI in the POI group and 30 healthy women in the control group (HC group), aged between 24 and 40 years, were recruited for this study. The transcriptomic profiles of peripheral blood samples from all study subjects were analyzed using RNA-sequencing. Results: The results revealed 39 differentially expressed genes in individuals with POI compared to healthy controls, with 10 upregulated and 29 downregulated genes. Correlation analysis highlighted the relationship between the expression of SLC25A39, CNIH3, and PDZK1IP1 and hormone levels. Additionally, an effective classification model was developed using SLC25A39, CNIH3, PDZK1IP1, SHISA4, and LOC389834. Functional enrichment analysis demonstrated the involvement of these differentially expressed genes in the "haptoglobin-hemoglobin complex," while KEGG pathway analysis indicated their participation in the "Proteoglycans in cancer" pathway. Conclusion: The identified genes could play a crucial role in characterizing the genetic foundation of POI, potentially serving as valuable biomarkers for enhancing disease classification accuracy.

Using Apparent Diffusion Coefficient (ADC) of Endometrial Cancer MRI to Determine P53 Molecular Subtypes.

BACKGROUND: Endometrial Cancer (EC) is a highly heterogeneous cancer comprising both histological and molecular subtypes. Using a non-invasive modality method to trigger these subtypes as early as possible can aid clinicians in establishing individualized treatment. PURPOSE: The study aimed to clarify the value of the Apparent Diffusion Coefficient (ADC) of EC MRI in determining molecular subtypes. MATERIAL AND METHODS: We retrospectively recruited 109 patients with pathologically proven EC (78 endometrioid cancers and 31 non-endometrioid cancers) with available molecular classification from a tertiary centre. MRI was prospectively performed a month prior to surgery; images were blindly interpreted by two experienced radiologists with consensus reading. The ADC value was measured by an experienced radiologist on the commercially available processing workstation. Interoperator measurement consistency was calculated. RESULTS: Our sample comprised 17 PLOE, 32 MSI-H, 31 NSMP, and 29 P53abn ECs. Clinical information did not differ significantly among the groups. The maximum diameter and volume of the lesions differed among the groups. The ADC value in the maximal area (ADCarea) or region of interest (ROI, ADCroi) in the P53abn group was higher than that in the other groups (894.0 ±12.6 and 817.5 ± 83.3 x10-6 mm2/s). The ADC mean values were significantly different between the P53abn group and the other groups (P = 0.000). The nomogram showed the highest discriminative ability to distinguish P53abn EC from other types (AUC: 0.859). CONCLUSION: Our results have suggested the quantitative MR characteristics (ADC values) derived from preoperative EC MRI to provide useful information in preoperatively determining P53abn cancer.

Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

Effects of oropharyngeal administration of own mother's milk on oral microbial colonization in very low birth weight infants fed by gastric tube: A randomized controlled trial.

AIMS: The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on oral microbial colonization in infants fed by gastric tube at different time points. METHODS: Infants (n = 116) with birth weight <1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The control group (n = 51) accepted oropharyngeal normal saline administration. The experimental group (n = 53) accepted oropharyngeal mother's milk administration before fed by gastric tube once every 3 h over 21 days after birth. We analyzed the oral microbiota at initiation and 7 and 14 and 21 days later using 16S DNA amplicon sequencing. RESULTS: There were no difference in oral microbial diversity between the two groups at any time point, but diversity decreased significantly over time in both groups. On the first day of life, the oral microbiota of the infant in the experimental and control groups consisted mainly of Firmicutes (7.75%, 6.18%) and Proteobacteria (68.65%, 68.69%), respectively. As time increases to 21 days after birth, Firmicutes (77.67%, 77.66%) had replaced Proteobacteria (68.65%, 68.69%) as the predominant phylum. DISCUSSION: From birth to 21 days after birth, oropharyngeal mother's milk administration did not change the diversity and structural composition of the oral microbiota. The oral microbial diversity of infants declined significantly over time. Firmicutes had replaced Proteobacteria as the predominant phylum.

SIRT3: A potential therapeutic target for liver fibrosis.

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

Determination of p53abn endometrial cancer: a multitask analysis using radiological-clinical nomogram on MRI.

OBJECTIVES: We aimed to differentiate endometrial cancer (EC) between TP53mutation (P53abn) and Non-P53abn subtypes using radiological-clinical nomogram on EC body volume MRI. METHODS: We retrospectively recruited 227 patients with pathologically proven EC from our institution. All these patients have undergone molecular pathology diagnosis based on the Cancer Genome Atlas. Clinical characteristics and histological diagnosis were recorded from the hospital information system. Radiomics features were extracted from online Pyradiomics processors. The diagnostic performance across different acquisition protocols was calculated and compared. The radiological-clinical nomogram was established to determine the nonendometrioid, high-risk, and P53abn EC group. RESULTS: The best MRI sequence for differentiation P53abn from the non-P53abn group was contrast-enhanced T1WI (test AUC: 0.8). The best MRI sequence both for differentiation endometrioid cancer from nonendometrioid cancer and high-risk from low- and intermediate-risk groups was apparent diffusion coefficient map (test AUC: 0.665 and 0.690). For all 3 tasks, the combined model incorporating all the best discriminative features from each sequence yielded the best performance. The combined model achieved an AUC of 0.845 in the testing cohorts for P53abn cancer identification. The MR-based radiomics diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). CONCLUSION: In the present study, the diagnostic model based on the combination of both radiomics and clinical features yielded a higher performance in differentiating nonendometrioid and P53abn cancer from other EC molecular subgroups, which might help design a tailed treatment, especially for patients with high-risk EC. ADVANCES IN KNOWLEDGE: (1) The contrast-enhanced T1WI was the best MRI sequence for differentiation P53abn from the non-P53abn group (test AUC: 0.8). (2) The radiomics-based diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). (3) The proposed model derived from multi-parametric MRI images achieved a higher accuracy in P53abn EC identification (AUC: 0.845).

Transcription factor PBX4 regulates limb development and haematopoiesis in mice.

The mammalian Pre-B cell leukaemia transcription factors 1-4 (PBX1-4) constitutes the PBC class of the homeodomain (HD)-containing proteins, which play important roles in diverse developmental processes. The functions and the underlying molecular mechanisms of PBX1-3 but not PBX4 have been extensively studied, and they have been reported to direct essential morphogenetic processes and organogenesis. In the present study, we generated knockin mice of FLAG-tagged PBX4 and the Pbx4 knockout (KO) mice and carried out in-depth characterisation of PBX4 expression and function. PBX4 was initially detected only in the testis among several organs of the adult mice and was expressed in spermatocytes and spermatids. However, no abnormality in spermatogenesis, but growth retardation and premature death after birth were observed in most adult Pbx4 KO mice. These animals were inactive and had shorter hindlimbs and lower numbers of reticulocytes and lymphocytes, probably caused by abnormalities at earlier developmental stages. Pbx4 mRNAs were indeed detected in several embryonic cell types related to limb development by in situ hybridisation and single-cell RNA-sequencing analysis. Pbx4 protein was also detected in the bone marrow of adult mice with a lower level compared with that in the testis. PBX4 preferentially binds to the promoters of a large number of genes including those for other HD-containing proteins and ribosomal proteins whose mutations are related to anaemia. PBX4-binding sites are enriched in motifs similar to those of other HD-containing proteins such as PKNOX1 indicating that PBX4 may also act as a co-transcription factor like other PBC proteins. Together, these results show that PBX4 participates in limb development and haematopoiesis while its function in spermatogenesis has not been revealed by gene KO probably due to the complementary effects of other genes.

Both intra- and peri-tumoral radiomics signatures can be used to predict lymphatic vascular space invasion and lymphatic metastasis positive status from endometrial cancer MR imaging.

OBJECTIVES: To identify lymphatic vascular space invasion (LVSI) and lymphatic node metastasis (LNM) status of endometrial cancer (EC) patients, using radiomics based on MRI images. METHODS: Five hundred and ninety-eight EC patients between January 2015 and September 2020 from two institutions were retrospectively included. Tumoral regions on DWI, T1CE, and T2W images were manually outlined. Radiomics features were extracted from tumor region and peri-tumor region of different thicknesses. We established sub-models to select features from each smaller category. Using this method, we separately constructed radiomic signatures for intra-tumoral and peri-tumoral images using different sequences. We constructed intra-tumoral and peri-tumoral models by combining their features, and a multi-sequence model by combining logits. Models were trained with 397 patients and validated with 170 internal and 31 external patients. RESULTS: For LVSI positive/LNM positive status identification, the multi-parameter MRI radiomics model achieved the area under curve (AUC) values of 0.771 (95%CI: [0.692-0.849])/0.801 (95%CI: [0.704, 0.898]) and 0.864 (95%CI: [0.728-1.000])/0.976 (95%CI: [0.919, 1.000]) in internal and external test cohorts, respectively. CONCLUSIONS: Intra-tumoral and peri-tumoral radiomics signatures based on mpMRI can both be used to identify LVSI or LNM status in EC patients non-invasively. Further studies on LVSI and LNM should pay attention to both of them.

Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis.

Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-ß (TGF-ß). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and Sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. siRNA experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Mo-doping heterojunction: interfacial engineering in an efficient electrocatalyst for superior simulated seawater hydrogen evolution.

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni0.85Se/MoSe2 heterostructural electrocatalyst, Mox-Ni0.85Se/MoSe2, was successfully prepared by simultaneously doping Mo cations into the Ni0.85Se lattice (Mox-Ni0.85Se) and growing atomic MoSe2 nanosheets epitaxially at the edge of the Mox-Ni0.85Se. Such an Mox-Ni0.85Se/MoSe2 catalyst requires only 110 mV to drive current densities of 10 mA cm-2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm-2. The experimental results, combined with the density functional theory calculations, reveal that the Mox-Ni0.85Se/MoSe2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni0.85Se can regulate the local electronic configuration of the Mox-Ni0.85Se/MoSe2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mox-Ni0.85Se/MoSe2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

The expression and diagnostic value of RARRES2, MACF1, and DCN in cerebrospinal fluid of patients with neurosyphilis / 中国医师杂志

Objective:To investigate the expression of retinoic acid receptor responsive gene 2 (RARRES2), microtubule microfilament cross-linking factor 1 (MACF1), and core protein polysaccharide (DCN) in cerebrospinal fluid (CSF) of patients with neurosyphilis, and their diagnostic value for neurosyphilis.Methods:A total of 64 non neurosyphilis syphilis patients (syphilis group) and 78 neurosyphilis patients (neurosyphilis group) admitted to the Second Hospital of Nanjing between June 2020 and September 2022 were included. Among neurosyphilis patients, there were 48 early neurosyphilis patients (early group) and 30 late neurosyphilis patients (late group). Patients with neurosyphilis are treated with routine symptomatic therapy and antibiotic therapy to expel syphilis. The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis before and after treatment were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients with neurosyphilis before and after treatment. The diagnostic value of various indicators for neurosyphilis was analyzed using receiver operating characteristic (ROC) curves.Results:The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis were higher than those in the syphilis group (all P<0.001). The mRNA levels of RARRES2, MACF1, and DCN in the CSF of patients with advanced neurosyphilis were higher than those in the early group (all P<0.001). Compared with before treatment, the NIHSS score and RARRES2, MACF1, and DCN mRNA levels of neurosyphilis patients decreased after treatment (all P<0.001). The area under the curve (AUC), sensitivity, and specificity of the combined diagnosis of RARRES2, MACF1, and DCN mRNA in CSF for neurosyphilis were 0.995%, 100.00%, and 93.75%, respectively. The AUC and sensitivity were higher than those of individual diagnosis. Conclusions:The expression of RARRES2, MACF1, and DCN is elevated in CSF of patients with neurosyphilis, and is associated with disease severity and treatment response. These three genes may be candidate biomarkers for diagnosing neurosyphilis.

Curative effect of full-femtosecond small incision lenticule extraction on the treatment of high myopia based on propensity score matching / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effect of full-femtosecond small incision lenticule extraction(SMILE)on the treatment of high myopia based on propensity score matching.METHODS: A total of 48 cases(48 eyes)of high myopia patients who underwent SMILE surgery in our hospital from May 2019 to May 2021 were selected as the observation group, and 48 cases(48 eyes)of high myopia patients who underwent FS-LASIK surgery were matched using propensity score matching as the control group. Follow up for 6mo after surgery, the changes in cylindrical, central corneal thickness, uncorrected visual acuity(UCVA), corneal endothelial cell related indicators [percentage of hexagonal endothelial cells(6A), coefficient of variation(CV)of endothelial cell area, central corneal endothelial cell density(ECD)] and corneal biomechanical indicators [simulated Goldman intraocular pressure(IOPg), corneal hysteresis(CH), corneal resistance factor(CRF), corneal compensated intraocular pressure(IOPcc)] between the two groups were compared, and the incidence of complications in both groups of patients was recorded.RESULTS: Both groups of patients showed significant improvements in cylindrical and UCVA at 3 and 6mo after surgery, as well as decreased central corneal thickness, corneal endothelial cells, and corneal biomechanics related indicators. The changes in the observation group were more significant(all P&#x003C;0.05). During the follow-up period, there was no significant difference in the incidence of complications between the observation group and the control group(8% vs. 17%, P&#x003E;0.05).CONCLUSION: SMILE has a definite effect on patients with high myopia and is helpful to improve visual acuity.

Effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on proteomics and autophagy in mice with type 2 diabetes mellitus induced by high-fat diet coupled with streptozotocin / 中国中药杂志

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.